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Tony L Yaksh: Influence Statistics

In rats stereotaxically implanted with microinjection cannula in either the periaqueductal gray matter (PAG) or the medial/paramedial medullary reticular formation (MRF), microinjection of morphine, sufentanil, D-Ala2-D-Leu5-enkephalin (DADL) or D-Ser2-Thr6-leucine enkephalin (DSTLE) produced dose-dependent elevations in the response latency on tail-flick and hot plate tests. These effects were reversed by naloxone administered by microinjection into the same intracerebral site. Both mu ...

Activation of p38 mitogen-activated protein kinase (p38) in spinal microglia is implicated in spinal nociceptive processing. Minocycline, a tetracycline derivative, displays selective inhibition of microglial activation, a function that is distinct from its antibiotic activity. In the present study we examined antinociceptive effects of intrathecal (IT) administration of minocycline in experimental models of inflammation-evoked hyperalgesia in addition to the effect of minocycline on ...

Tumor necrosis factor-alpha (TNF) is upregulated after nerve injury, causes pain on injection, and its blockade reduces pain behavior resulting from nerve injury; thus it is strongly implicated in neuropathic pain. We investigated responses of intact and nerve-injured dorsal root ganglia (DRG) neurons to locally applied TNF using parallel in vivo and in vitro paradigms. In vivo, TNF (0.1-10 pg/ml) or vehicle was injected into L5 DRG in naive rats and in rats that had received L5 and L6 ...

High pressure liquid chromatography with electrochemical detection was used to quantify the efflux, in the same sample, of endogenous 5-hydroxytryptamine (5-HT), noradrenaline (NA), and 5-hydroxyindoleacetic acid (5-HIAA) into superfusates of the rat spinal cord in vivo. The efflux of these three agents was measured prior to, and during, electrical stimulation of the nucleus raphe magnus (n.r.m.) and nucleus reticularis paragigantocellularis (n.r.p.g.), two medullary nuclei implicated in ...

Western blots show the constitutive expression of COX-1 and COX-2 in the rat spinal dorsal and ventral horns and in the dorsal root ganglia. Using selective inhibitors of cyclooxygenase (COX) isozymes, we show that in rats with chronic indwelling intrathecal catheters the acute thermal hyperalgesia evoked by the spinal delivery of substance P (SP; 20 nmol) or NMDA (2 nmol) and the thermal hyperalgesia induced by the injection of carrageenan into the paw are suppressed by intrathecal and ...

Transient spinal cord ischemia may lead to a progressive degeneration of spinal interneurons and subsequently to increased hind limb motor tone. In the present work we sought to characterize the rigidity and spasticity components of this altered motor function by: i) tonic electromyographic activity measured in gastrocnemius muscle before and after ischemia, ii) measurement of muscle resistance during the period of ankle flexion and corresponding changes in electromyographic activity, ...

Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a ...

We studied the effect of thoracic aortic occlusion and cerebrospinal fluid (CSF) drainage on regional spinal cord blood flow and its correlation with neurologic outcome. Using isotope-tagged microspheres, we determined blood flow to the gray and white matter of five regions of the spinal cord in dogs: group I (control), group II (cross-clamp only), group III (cross-clamp plus CSF drainage). At 60 minutes after thoracic aortic occlusion in group II, median gray matter blood flow (GMBF) in ...

Injection of formalin into the hind paw evokes a biphasic flinching of the injured paw. Pharmacological characterization of this behavior has implicated the spinal release of excitatory amino acids (EAAs) and cyclooxygenase (COX) products. To address this hypothesis, we examined the effect of paw formalin injection on release of EAAs and prostaglandin E2-like immunoreactivity (PGE2-LI) from the spinal cord in unanesthetized rats using a dialysis probe placed in the lumbar subarachnoid ...

Intrathecally administered mu-opioid (morphine; DAMGO ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin)) and delta-opioid (DPDPE ([D-Pen2,D-Pen5] enkephalin); DADLE ([D-Ala2,D-Leu5]enkephalin)) receptor preferring agonists were systematically challenged with the competitive opiate antagonists naloxone or naltrindole in the rat. Naloxone produced a dose-dependent reduction in agonist effect with the intrathecal IC50 being similar for all agonists (2.1-5.4 micrograms). In contrast, the naltrindole ...

1. In the present study, the object was to examine the effects of morphine on spinal release in vivo of excitatory amino acids (EAA), prostaglandin E2 (PGE2), and a marker for nitric oxide (NO) synthesis, citrulline (Cit), evoked by a protracted noxious stimulus produced by the injection of formalin into the paw. Spinal release was monitored in conscious rats using a microdialysis probe implanted into the subarachnoid space with the active site placed at the level of the lumbar ...

BACKGROUND: Noxious cutaneous stimuli enhance spinal excitability. The behavioral correlate to this response is found in the rat formalin test, in which formalin injection into the hindpaw evokes signs of nociception (flinching and licking of the injected paw) with acute (phase 1) and delayed-hyperalgesic (phase 2) components.

METHODS: The effect of intrathecal morphine (a mu agonist), U50488H (a kappa agonist), ST-91 (an alpha 2 agonist), L-PIA (an adenosine A1 agonist), and ketorolac ...